Vedolizumab + Cyclophosphamide + Tacrolimus for Graft-versus-Host Disease

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Herbal medications, others

Disqualifiers: Prior allogeneic HCT, active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 181

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of three medications—vedolizumab (a type of immunotherapy), cyclophosphamide, and tacrolimus—can prevent graft-versus-host disease (GVHD) in patients undergoing a specific type of stem cell transplant. GVHD occurs when transplanted donor cells attack the patient's healthy cells. The trial targets individuals undergoing an allogeneic hematopoietic cell transplant (a procedure involving donor stem cells) after receiving lower doses of chemotherapy. This trial may suit those in remission from certain blood cancers, such as acute leukemia or myelodysplastic syndrome, who qualify for this type of transplant. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those taking other investigational drugs for GVHD prophylaxis and herbal medications. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vedolizumab is generally safe for patients. In studies, it caused few side effects related to graft-versus-host disease (GVHD) in people receiving stem cell transplants, meaning most patients did not experience major issues.

Trial data suggest that cyclophosphamide is effective and safe for preventing GVHD. It is commonly used in treatment plans for transplant patients, with no unusual safety concerns reported.

Tacrolimus is another medication used to prevent GVHD. Studies have shown it is safe and effective when used as directed. It helps control the immune system to stop it from attacking healthy cells.

In summary, previous studies have shown that the combination of vedolizumab, cyclophosphamide, and tacrolimus is safe, with few serious side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for graft-versus-host disease, which primarily involve steroids and other immunosuppressants, vedolizumab targets a specific protein that helps control inflammation in the gut. This targeted approach can potentially reduce the side effects commonly associated with broader immunosuppressive drugs. Researchers are excited about vedolizumab because it could offer a more precise method to manage graft-versus-host disease, potentially improving outcomes and quality of life for patients undergoing allogeneic stem cell transplants.

What evidence suggests that this trial's treatments could be effective for preventing graft-versus-host disease?

Research has shown that vedolizumab, a monoclonal antibody, effectively prevents gut symptoms of acute graft-versus-host disease (aGVHD). It blocks certain immune cells from entering the intestines, reducing inflammation. In this trial, participants will receive a combination of vedolizumab, cyclophosphamide, and tacrolimus. Cyclophosphamide, commonly used in cancer treatments, weakens the immune system to prevent the body from attacking itself. Tacrolimus suppresses the immune system by stopping certain immune cells from becoming active. Together, these treatments have shown promise in lowering the risk of GVHD in patients receiving stem cell transplants. ^{6 7 8 9 10}

Who Is on the Research Team?

Monzr M. Al Malki

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers or disorders who are undergoing a stem cell transplant from a donor after receiving lower doses of chemotherapy. It aims to prevent the immune response where transplanted cells attack the patient's body (GVHD).

Inclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative

* Assent, when appropriate, will be obtained per institutional guidelines

* Agreement to allow the use of archival tissue from diagnostic tumor biopsies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Conditioning

Participants receive reduced intensity conditioning with fludarabine and melphalan before transplantation

1 week

Daily visits for conditioning

Transplantation and Initial Treatment

Participants undergo allogeneic HCT and receive vedolizumab, cyclophosphamide, and tacrolimus

14 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up visits at day +180 and 1 year post-HCT

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Tacrolimus
• Vedolizumab

Trial Overview The study tests if vedolizumab, combined with cyclophosphamide and short-term tacrolimus after transplant, can prevent GVHD in patients receiving reduced intensity conditioning before allogeneic hematopoietic cell transplantation.

How Is the Trial Designed?

Group I: Prevention (vedolizumab, cyclophosphamide, tacrolimus) Experimental Treatment 12 Interventions

Patients receive reduced intensity conditioning with fludarabine IV on days -7 to -3 and melphalan IV on day -2. Patients then undergo allogeneic HCT on day 0. Patients also receive vedolizumab IV over 30 minutes on days -1, +13, +41, +69, +97, +125, and +153, cyclophosphamide IV on days +3 and +4, and tacrolimus IV or PO on day +5 to day +95 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT and ECHO or MUGA during screening, blood sample collection on study, and bone marrow biopsy throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

High-dose cyclophosphamide used as a single-agent prophylaxis after myeloablative allogeneic bone marrow transplantation significantly reduced the incidence of acute graft-versus-host disease (GVHD), with rates of 43% for grades II-IV and 10% for grades III-IV among 117 patients.

The treatment also demonstrated promising long-term outcomes, with a 2-year overall survival rate of 55% and a low cumulative incidence of chronic GVHD at 10%, indicating its efficacy and safety in patients with advanced hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Luznik, L., Bolaños-Meade, J., Zahurak, M., et al.[2022]

A patient with severe graft versus host disease (GVHD) after a bone marrow transplant showed no improvement with standard treatments like cyclosporine and high-dose steroids.

However, treatment with tacrolimus and Psoralen plus ultraviolet light (PUVA) led to complete resolution of GVHD symptoms, suggesting this combination could be effective for other patients with treatment-resistant GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful therapy of refractory graft versus host disease with tacrolimus and Psoralen plus ultraviolet light. Jubran, RF., Dinndorf, PA.[2019]

Tacrolimus has been found to be effective in preventing graft-versus-host disease (GVHD) in patients undergoing allogeneic bone marrow transplants, highlighting its potential as a critical intervention in this high-risk population.

Further research is necessary to refine dosage schedules and establish therapeutic ranges to ensure both efficacy and safety in the use of tacrolimus for GVHD prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus: an alternative for graft-versus-host disease prevention. Lee, TJ., Kennedy, LA.[2017]

A study of 2,905 patients who developed grade II-IV acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation showed a significant decrease in the proportion of severe grade III-IV GVHD over time, from 56% in 1999-2001 to 37% in 2006-2010.

Patients treated with tacrolimus-based prophylaxis experienced notable improvements in overall survival and reduced treatment-related mortality, particularly among those with grade II acute GVHD, indicating that this treatment regimen may enhance outcomes for transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival after acute graft-versus-host disease diagnosis in the modern era. Khoury, HJ., Wang, T., Hemmer, MT., et al.[2019]

Citations

1. withpower.com withpower.com/trial/vedolizumab-cyclophosphamide-tacrolimus-for-graft-versus-host-disease-5f0b4

Vedolizumab + Cyclophosphamide + Tacrolimus for Graft- ... Research shows that Vedolizumab is effective for treating gastrointestinal symptoms of graft-versus-host disease, and Tacrolimus has been successful in ...

2. nature.com nature.com/articles/s41591-024-03016-4

Vedolizumab for the prevention of intestinal acute GVHD ... There was a statistically significant difference favoring vedolizumab over placebo for lower-GI aGVHD-free and relapse of the underlying ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00341

Vedolizumab Plus Post-transplant Cyclophosphamide and ... This phase II trial studies how well vedolizumab plus post-transplant cyclophosphamide (PTCy) and short course tacrolimus work for the prevention of graft ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6963235/

Vedolizumab for prevention of graft-versus-host disease after ... Vedolizumab could help prevent aGVHD by inhibiting the migration of both naive and activated lymphocytes into gut-associated lymphoid tissues ...

5. ashpublications.org ashpublications.org/blood/article/142/12/1037/496953/Novel-developments-in-the-prophylaxis-and

Novel developments in the prophylaxis and treatment of acute ... TAC/MTX led to a lower incidence of grade 2 to 4 aGVHD and extensive chronic GVHD (cGVHD), when compared with CSA/MTX in MRD allo-HCT.8 In MUD ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10558021/

Post-Transplant Cyclophosphamide for the Prevention of ... Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503189

Graft-versus-Host Disease Prophylaxis with ... Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00856

Post-Transplant Cyclophosphamide-Based Graft-Versus ... PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless ...

9. link.springer.com link.springer.com/article/10.1007/s00277-025-06657-8

Safety and feasibility of intermediate-dose post-transplant ... Safety and feasibility of intermediate-dose post-transplant cyclophosphamide for graft-versus-host disease prophylaxis. Case Report; Open ...

10. nature.com nature.com/articles/s41375-024-02445-x

Post-transplant cyclophosphamide separates graft-versus ... Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001).